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Pseudo-epidermis: A model system for investigating molecular and cellular pathways of cutaneous epidermal toxicity from sulfur mustard

Technical Report ·
OSTI ID:7117618
; ; ; ;
Damage to DNA, Inhibition of DNA replication and mitosis, appearance of abnormal keratin peptide and large differentiated cells and, finally, death of cells occur dose- and time-responsively in submerged cultures of keratinocytes exposed to bis-(b-chloroethyl)sulfide (BCES). However, the relevance of these parameters to vesication in human skin exposed to mustard in vivo has yet to be established. The pseudo-epidermis cultured from human cutaneous keratinocytes offers a system in which the pathogenic importance of each of these parameters can be evaluated. To establish the validity of the system, it is necessary to show that the pseudo-epidermis undergoes similar dose- and time-dependent cytotoxicity from BCES as is observed in the human skin after topical exposure to the mustard. This report includes data which demonstrate a dose- and time-dependent destruction of the germinative layer in human pseudo-epidermis after topical application of BCES. In addition, data are included to show that DNA is a primary target for BCES in pseudo-epidermis as it is in vivo. Also included in this report is a proposed sequence of molecular and cellular events to account for cytotoxicity in the germinative population of the pseudo-epidermis after exposure to BCES.
Research Organization:
Michigan Univ., Ann Arbor, MI (United States)
OSTI ID:
7117618
Report Number(s):
AD-P-008762/7/XAB
Country of Publication:
United States
Language:
English

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45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEFENSE
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